This article was written as part of my Science Journalism elective taught by Jonathan Weiner in Fall 2011. Our assignment was to go to a lab and write a feature story using narrative techniques and the ability to translate science for readers.
There’s no place like home: Portrait of a lab
By Anne Cohen
As the daughter of a scientist, there is something inherently comforting to me about walking into a lab. They all have that familiar smell of phenol and chloroform – dull with sharp undertones, and almost sweet. Dr. Stephen Goff’s lab is no different.
When you exit the elevator on the 13th floor in the Hammer Building of the Columbia Medical Center, early in the day, the white and grey diamond formica tiles lead the way down sinuous hallways, punctuated with quiet laboratories and equipment rooms.
The loud whirring of the generators and refrigerators are soothing in the silence of the morning. Ten o’clock is still too early for most; scientists keep peculiar hours. Inside one of the labs, sits Angela Eruzo, a post doctorate student who has been at the lab for a year. She laughs. “One of the few perks of the job is that you kind of make your own hours,” she says. “It’s very flexible but sometimes you feel like you’re never really off work.”
Each bench, or workstation, has the same layout: Long blue counter, white cabinets. Some drawers bear fraying, yellow labels with names like “Tools”, “Radioactivity supplies,” and “Cuvettes.” Some drawers have only the yellow imprint of labels long gone. Over the counters are 5 shelves that go almost up to the ceiling. These are filled with glass solution containers, electric generators, centrifuges, cables, binders, notebooks. There is no space to waste.
Eruzo peeks through the cluttered shelves at Gloria Arriagada, another post-doctorate student from Chile, hunched over her computer. “It’s great! Through the shelves you can spy on people,” she whispers.
There is no food or drink allowed at the benches; that’s what the lunchroom down the hall is for. Of course, exceptions are made: Arriagada slides open her desk drawer to reveal a bottle of water. “I need a coffee!” she says. “Do you want a coffee?” She leads me into the lunchroom, a small room with a couch, a table and six chairs. The back wall is stacked with old issues of Nature magazine.
Arriangada opens the fridge, which looks filled with the culinary version of what lies in the refrigerators in the equipment room – glass bottles, full of hoisin and soya sauce rather than cells and viruses. Arriangada washes her coffee mug, wipes it and sets it on the counter. She explains that there used to be a dish rack, but it was removed because people let their dishes lie around for too long. “It’s like living with many many roommates!” she says, rolling her eyes.
As far as second homes go, this one has a rather strange occupation, in definite contrast with the domestic environment. Goff’s lab focuses on retrovirus replication. This means that he and his colleagues look at the very basic aspects of how the Human immunodeficiency virus (HIV) and leukemia viruses work and how they interact with viral proteins.
“We think of them as little machines,” Goff said.
A virus is a tiny infectious agent that can only replicate inside living cells. The virus itself is made up of three parts: molecules of viral ribonucleic acid (RNA) or deoxyribonucleic acid (DNA); a protein coat that surrounds these genes; and a layer of lipids that protects the virus outside of a cell.
In order to spread, viruses need to replicate. To do that, they need to enter the cell, and leave a little bit of themselves inside – DNA. Once the cells grow and multiply, so does the viral DNA inside them, allowing the virus to spread inside its host.
Goff and his colleagues are currently studying expressed RNA. RNA viruses are integrated into the host DNA. That altered DNA is then replicated and spreads. Cellular proteins play a big part in that process.
“We’ve come to understand that viruses make use of many many proteins. They borrow them, and subvert them,” Goff said.
Goff’s lab is a medium sized one: five graduate students, eight post-doctorate students.
He tries to keep it about half and half. Each student has a number of experiments and projects they are working on at one time; they juggle those assignments while writing papers.
“ The closest analogy is being a chef, being a cook,” Goff said.
If that is the case, then Goff is Mario Batalli. With scruffy white hair, a white beard, and youthful eyes, Goff casts a fatherly shadow over his lab. Goff was a graduate student in Paul Berg’s lab at Stanford University when they were studying recombinant DNA- DNA sequences that bring together genetic material from multiple sources in the mid-70s. He then did a post-doctorate degree in David Baltimore’s lab at MIT, where he started doing work on RNA retroviruses. He has been at Columbia University since 1981.
When I email him to ask to speak to him about the lab, he replies: “Why don’t I send you into the trenches.”
The “trenches” are two doors down the hall from Goff’s office.
Despite Eruzo’s playful enthusiasm, she is working on serious stuff. She, in collaboration with Jason Rodriguez, another lab colleague, is working to screen for cell protein implications on HIV replication. They are examining what kinds of conditions are needed to silence the proteins, then apply those conditions to the cells and see the effect they have on HIV replication. When the proteins are removed from the equation, their actual role becomes more clear.
“Just a bunch of questions,” Eruzo says. “What regions of protein are important? At what stage are they important? Why? Why?”
Eruzo sits at her bench, preparing for an experiment. She is working on a method to separate proteins based on size. Protein 131 has equal numbers of cells. If you add viral RNA, it quiets the protein expression, and after some time, stops it completely. Eruzo is testing how long it will take to completely quiet protein expression. This is called optimization.
“It smells like rotten eggs,” Eruzo says, as she stirs in the sample buffer. This will stop metabolic processes and denature the proteins.
The next step is to boil them to stop the cells from degrading any further.
Eruzo was born and raised in Sunset Park, Brooklyn. “In the corner building on 4th Avenue,” she says. “You didn’t have to watch TV, there was always drama outside.”
She did her undergraduate degree at Brooklyn College, and then went to the University of Pittsburg for graduate school. After doing a post-doctorate degree at Mount Sinai in New York, she came to Goff’s lab.
Along with her everyday work, Eruzo juggles her own pet project: the Matrin 3 protein. She’s been working on it since graduate school.
The Matrin 3 protein is one of the twelve proteins that make up the matrix of the cell nucleus.
“It’s kind of like a skeleton for the nucleus,” Eruzo explains.
Other research has already found that what happens in the cell nucleus has an impact on HIV. Eruzo wants to figure out the other effects that this protein has on HIV.
Eruzo is concentrating as she scrapes the cells by stirring them quickly, then transfers the purple cell solution, the same color as her indigo gloves, into plastic test tubes.
Through the silence, the shuffling of feet as people bump into each other in the cramped space is interspersed with beeps from timers, and the occasional sigh.
When asked how to know when to stop scraping the cells, Eruzo giggles. “It’s not the most scientific method,” she says. “I just try to do it until I think all the cells are off.”
The point of all this prep is to create an electric wave. Eruzo takes out a glass rectangular container with an electrode on each side, and fills it with water. On each side, there are two green combs, with little wells in between the teeth. Eruzo meticulously loads in her samples into each well. Once the proteins have separated, she can use bands that turn various shades of blue to determine the protein standards.
Eruzo plugs in black and red cables —attached to the electrodes — into the electrophorysis power supply. Bubbles start to rise as the electricity flows through the container.
“And then we wait,” says Eruzo.
Eruzo’s long brown hair is tied in a braid while she works. Mornings are her favorite time in the lab, because there is no one around, and therefore no wait to use the equipment.
When I ask her what she finds comforting in a lab environment, she blushes. “It’s kind of corny but the hum of the culture hoods,” she replies.
Though the hours are long and it sometimes feel like she’s never away from her work, Eruzo says it’s worth it for the thrill. “ I guess you always feel a sense of urgency. It’s never really fast enough and if things are going badly you feel guilty for going away. There’s a really great surge of happiness when you do get a good result because it almost never happens,” she says, only half joking.
When I return to the lab two weeks later, it is late afternoon. The halls are still quiet, but inside the lab, there is a flurry of activity as people prepare their final experiments of the day.
I walk into the kitchen, where Sedef Onal, a graduate student from Turkey, is rummaging through the fridge. The whiteboard at the back of the room reads: “Today the maid took the day off. Clean your dirty dishes and put it away: plates, forks, knives, mugs, coffee grounds/cup.”
“I was going to smoke a cigarette, wanna come?” Onal asks. She leads me out of the building to the street behind, where she has her spot picked out. There is even a ledge so she can put down her coffee mug.
Onal is in her 3rd year as a graduate student and decided to join Goff’s lab a year and a half ago after a series of rotations graduate students go through many labs for a short period of time before deciding where to settle.
When I ask why she chose this particular lab, she looks around, and then replies: “ I’ve been doing biology for 10 years now and I have not dissected a single mouse and I’d like to keep it that way. I can do that here.”
Onal is looking at the interactions between two host proteins and the effect those genes have on HIV. Her preliminary data indicates that both those genes increase the HIV-1 exit stage- HIV can enter and exit cells through the cell membrane — but she allows that this could be due to an experimental artifact.
After finishing her undergraduate degree at the University of California Irvine in 2004, Onal returned to Turkey where she got a masters degree in bio-science and bio-engineering. She then worked at a hospital in clinical genetic diagnosis for two years, but found the work repetitive and boring. She wanted to get back to research, and so came back to the United States in 2009.
Today, Onal is using a plasmid —a DNA molecule that can replicate independently — that makes all viral proteins sufficient, so they can be expressed in cell, and then creates a virus-like particle that can butt out of the cell, which models the exit phase of HIV-1 infection. She will give that plasmid to cells with either one of the two genes that she is looking at, and then she does a control experiment with cells that do not have those genes to see what’s the difference in the HIV-1 proteins that are being produced and butting out.
To make sure that the positive effect she has already observed is correct, and that her genes are increasing the take-up of the DNA into the cell, she is using a plasmid that shouldn’t have any important role in the cell. This will allow her to see if her proteins will also raise the levels of the unrelated plasmid.
Onal spends the next 25 minutes flitting back and forth between the tissue culture room, where the cells are grown and stored, and a computer room where the data will be analyzed.
With dyed auburn hair, a black sweatshirt, and grey shorts over black tights, Onal looks more like a quirky college student than a scientist. Her favorite book is A Hitchiker’s Guide to the Galaxy, and she’s seen every episode of Firefly, a “space western” television series. But she is passionate about her work. Something about being in a lab just makes her tick. “It’s the excitment of being frustrated for months then getting a positive result. I like the puzzle of it I guess.”
Onal confides that her favorite time to work is at night. To make her point, she points to her coffee mug, which reads “Mornings aren’t magical.” When no one is around, she can go a little crazy. “When it’s quiet and there’s no one else I can blast the music and dance around the lab without looking weird,” she says.
Though Onal misses the lab — and the restless anxiety of research — when she’s away too long, there are exceptions. She smiles slyly and leans in conspiratorially: “Like last week I was in Cali and I didn’t miss the lab at all!”
As it gets later, some people start filtering out of the lab, either to go home, or to eat to fuel for a long night. The work goes on. As Stephen Goff says, “We’ve got more than enough to keep us all very busy for a long time.”